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Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

Mondy, Kristin Ea,b; de las Fuentes, Lisaa; Waggoner, Alana; Önen, Nur Fa; Bopp, Coco Sa; Lassa-Claxton, Sherrya; Powderly, William Gc; Dávila-Román, Victora; Yarasheski, Kevin Ea

doi: 10.1097/QAD.0b013e3282f70694
Clinical Science

Objective: Cardiovascular disease risk among persons with HIV is likely multifactorial, thus testing a variety of available noninvasive vascular ultrasound and other surrogate tests may yield differing results. To address this issue, we assessed multiple metabolic and clinical predictors of endothelial function and carotid intima–media thickness in HIV-infected subjects and compared results with HIV-negative controls.

Design: Prospective, cross-sectional study of 50 HIV-infected, healthy adults on stable highly active antiretroviral therapy matched to 50 HIV-negative controls by age, sex, race, and body mass index.

Methods: Flow-mediated vasodilation of the brachial artery, carotid intima–media thickness, dual energy X-ray absorptiometry (HIV-infected subjects), and fasting insulin, lipids, and oral glucose tolerance tests were performed. Results were compared between HIV-infected and control groups.

Results: Fifty percent of subjects were African–American with 34% women. Among HIV-infected, mean CD4 cell count was 547 cells/μl; 90% had HIV RNA less than 50 copies/ml. There were no significant differences between HIV-infected and control subjects with regard to brachial artery flow-mediated vasodilation or carotid intima–media thickness. In multivariate analyses of the HIV cohort, independent predictors of endothelial dysfunction (lower flow-mediated vasodilation) were increasing insulin resistance, greater alcohol consumption, and higher baseline brachial artery diameter (P < 0.05); predictors of increased carotid intima–media thickness were hypertension, higher trunk/limb fat ratio, and insulin resistance (P < 0.05).

Conclusion: In this HIV cohort on modern highly active antiretroviral therapy with well controlled HIV, there were no significant differences with regard to preclinical markers of cardiovascular disease. Insulin resistance was a strong predictor of impaired brachial artery flow-mediated vasodilation and increased carotid intima–media thickness, and may be an important cardiovascular disease risk factor in the HIV population.

From the aWashington University School of Medicine, USA

bJohn Cochran Veterans Affairs Medical Center in St Louis, St Louis, Missouri, USA

cUniversity College Dublin School of Medicine and Medical Science, Dublin, Ireland.

Correspondence to Kristin Mondy, MD, Division of Infectious Diseases, Washington University School of Medicine, 660 S Euclid, Campus Box 8051, St Louis, MO, USA. Tel: +1 314 747 1725; fax: +1 314 454 5392; e-mail: kmondy@im.wustl.edu

© 2008 Lippincott Williams & Wilkins, Inc.